Evidence map›Paper›PMID 28547925›Full record

ArticleBritish journal of pharmacology2017

The saponin D39 blocks dissociation of non-muscular myosin heavy chain IIA from TNF receptor 2, suppressing tissue factor expression and venous thrombosis.

Ke-Feng Zhai, Jin-Rong Zheng, You-Mei Tang, Fang Li, Yan-Ni Lv, Yuan-Yuan Zhang, Zhen Gao, Jin Qi, Bo-Yang Yu, Jun-Ping Kou

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 70 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Ke-Feng ZhaiState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.ORCID http://orcid.org/0000-0002-5198-4332
Jin-Rong ZhengState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
You-Mei TangState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Fang LiState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Yan-Ni LvState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Yuan-Yuan ZhangState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Zhen GaoDepartment of Medicine-Ather&Lipo, Baylor Colledge of Medicine, Houston, TX, USA.
Jin QiState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Bo-Yang YuState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Jun-Ping KouState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
China Pharmaceutical University · CNBaylor College of Medicine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeNon-muscular myosin heavy chain IIA (NMMHC IIA) plays a key role in tissue factor expression and venous thrombosis. Natural products might inhibit thrombosis through effects on NMMHC IIA. Here, we have shown that a natural saponin, D39, from Liriope muscari exerted anti-thrombotic activity in vivo, by targeting NMMHC IIA. EXPERIMENTAL APPROACH: Expression and activity of tissue factor in endothelial cells were analysed in vitro by Western blot and simplified chromogenic assays. Interactions between D39 and NMMHC IIA were assessed by serial affinity chromatography and molecular docking analysis. D39-dependent interactions between NMMHC IIA and TNF receptor 2 (TNFR2) were measured by immunofluorescence, co-immunoprecipitation and proximity ligation assays. Anti-thrombotic activity of D39 in vivo was evaluated with a model of inferior vena cava ligation injury in mice. KEY

resultsD39 inhibited tissue factor expression and procoagulant activities in HUVECs and decreased thrombus weight in inferior vena cava-ligated mice dose-dependently. Serial affinity chromatography and molecular docking analysis suggested that D39 bound to NMMHC IIA. In HEK293T cells, D39 inhibited tissue factor expression evoked by NMMHC IIA overexpression. This effect was blocked by NMMHC IIA knockdown in HUVECs. D39 inhibited dissociation of NMMHC IIA from TNFR2, which subsequently modulated the Akt/GSK3β-NF-κB signalling pathways. CONCLUSIONS AND IMPLICATIONS: D39 inhibited tissue factor expression and thrombus formation by modulating the Akt/GSK3β and NF-κB signalling pathways through NMMHC IIA. We identified a new natural product that targeted NMMHC IIA, as a potential treatment for thrombotic disorders and other vasculopathies.

Indexed as

Fibrinolytic AgentsSaponinsAnimalsCells, CulturedGlycogen Synthase Kinase 3 betaHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsMaleMice, Inbred C57BLMolecular Docking SimulationMyosin Heavy ChainsProto-Oncogene Proteins c-aktReceptors, Tumor Necrosis Factor, Type IIThromboplastinTranscription Factor RelAFibrinolytic AgentsGlycogen Synthase Kinase 3 betaGSK3B protein, humanMyosin Heavy ChainsProto-Oncogene Proteins c-aktReceptors, Tumor Necrosis Factor, Type IISaponinsThromboplastinTranscription Factor RelATumor Necrosis Factor-alpha

Identifiers

PMID28547925
PMCPMC5554322
OpenAlexW2800194932

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.